Reviews

This article summarizes the current management of patients with newly diagnosed cervical cancer. The topics range from the management of early-stage disease to the phase III randomized studies that have established the current standard of care for patients with locally advanced cancer of the cervix. New approaches to combined-modality therapy with the goal of improving outcomes and decreasing complications are also described.

Worldwide, carcinoma of the cervix is the second most common cancer in women, with an incidence of approximately 500,000 new cases each year and an annual death rate approaching 200,000; many of these women present with advanced-stage disease.[1] Cervical cancer is less prevalent in the United States, but still accounted for over 10,000 new cases and 3,700 deaths in 2005 alone.[1]

Background

The management of patients diagnosed with cervical cancer is determined foremost by clinical stage at presentation, using the International Federation of Gynecology and Obstetrics (FIGO) staging system (Table 1). Surgery is commonly recommended for the definitive management of patients presenting with stage IA disease. The risk of recurrence following curative surgery for patients with stage IA disease is less than 1%.[2] The procedure consists of an extrafascial hysterectomy for stage IA1 disease or radical hysterectomy with pelvic lymph node dissection and possible para-aortic lymph node sampling for stage IA2 and higher. Patients with stage IA1 disease who are not surgical candidates or who desire to preserve fertility may be managed with a cone biopsy alone if negative margins can be obtained.

Prior to the 1990s, patients with stage IIB or higher advanced disease were treated with radiation alone. However, high rates of recurrence were noted both in the pelvis and distantly. In one series, nearly two-thirds of women treated with radiation alone had recurrent disease in the pelvis; these treatment failures were associated with higher rates of distant metastasis.[3]

Investigators attempted to improve upon these results with the addition of chemotherapy. Early studies examined the role of neoadjuvant chemotherapy followed by radiation. Unfortunately this treatment did not translate into an improvement in cure rates. In fact, one study even showed decreased overall survival.[4-10] Preliminary studies of concurrent chemoradiation (chemotherapy and radiation given simultaneously) demonstrated more promise and led to several US phase III trials (Table 2).[11-15] These studies demonstrated between a 30% and 50% survival benefit for concurrent cisplatin-based chemoradiation in locally advanced cervical cancer.

It should be noted that a single study from Canada (not listed in Table 2) failed to document a benefit of chemoradiation compared to radiation alone.[16] However, radiotherapy in this study was administered over a shorter period of time (median: 51 days) compared to other studies (62 to 64 days) and the study was not statistically powered to detect survival differences of less than 15%, a weakness noted by the authors.

Based on the results of these studies, the National Cancer Institute issued a clinical announcement in 1999 urging that strong consideration be given to treating patients diagnosed with invasive cervical cancer with concurrent platinum-based chemoradiation.[17] Despite this clinical announcement, the optimal management of patients diagnosed with stage IB1/IIA cervical cancer is still controversial. These patients may be managed with definitive surgery, definitive chemoradiation, or a combination of surgery and radiation with or without chemotherapy. Patients presenting at these stages are typically managed based on individual factors (eg, comorbidities, age, patient preference) and institutional expertise.

No randomized trial in the United States has compared definitive radiation therapy to radical hysterectomy for patients with stage IB/IIA cervical cancer. In Italy, Landoni and colleagues performed a study to address this question. Patients were randomized to either radical hysterectomy or radiation therapy, and there were no differences in overall survival. However, patients randomized to the surgery arm received adjuvant radiation if final pathology demonstrated extensive disease.[18] Severe complications, defined as morbidities requiring medical or surgical management, were significantly higher in the surgery group (28% vs 12%), and even more so in the patients who received both surgery and radiation. This study has also been criticized for the high rates of complications seen with surgery alone.